Identification of Novel Somatic Fusions of , and in Prostate Cancer Treated with Anlotinib and Androgen Deprivation Therapy: A Case Report

Overview

Journal Cancer Innov

Specialty Biomedical Engineering

Date 2023 Dec 13

PMID 38089454

Authors

Qiuli Liu

Shuo Wang

Ze Wang

Peng Tang

Dianzheng Zhang

Weihua Lan

Jun Jiang

Affiliations

Soon will be listed here.

Abstract

The fusion gene has frequently been found in prostate cancer and is associated with malignancy. Identifying novel fusions will help to stratify patients and establish patient-tailored therapies. A 78-year-old man presented to our hospital with severe symptoms of urinary urgency and frequency for 2 years, as well as severe bone pain for 1 year. He was diagnosed with metastatic prostate cancer with a Gleason score of 5 + 5. Three gene fusions, , , and , were identified in the patient's prostate cancer tissue. Notably, administration of the tyrosine kinase inhibitor, anlotinib, in combination with a gonadotropin-releasing hormone agonist (GnRHa) and abiraterone, reduced the patient's bone pain and also stabilized his prostate cancer for more than 2 years. This is the first report of somatic fusions among the , , and genes in cancer tissues from a patient with prostate cancer who responded well to antiangiogenic treatment combined with a GnRHa and abiraterone.

Citing Articles

Identification of novel somatic fusions of , and in prostate cancer treated with anlotinib and androgen deprivation therapy: A case report.

Liu Q, Wang S, Wang Z, Tang P, Zhang D, Lan W Cancer Innov. 2023; 1(1):114-118.

PMID: 38089454 PMC: 10686182. DOI: 10.1002/cai2.11.

References

Ioannidou E, Moschetta M, Shah S, Parker J, Ozturk M, Pappas-Gogos G . Angiogenesis and Anti-Angiogenic Treatment in Prostate Cancer: Mechanisms of Action and Molecular Targets. Int J Mol Sci. 2021; 22(18). PMC: 8472415. DOI: 10.3390/ijms22189926. View

Park K, Dalton J, Narayanan R, Barbieri C, Hancock M, Bostwick D . TMPRSS2:ERG gene fusion predicts subsequent detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia. J Clin Oncol. 2013; 32(3):206-11. PMC: 3887478. DOI: 10.1200/JCO.2013.49.8386. View

Klezovitch O, Risk M, Coleman I, Lucas J, Null M, True L . A causal role for ERG in neoplastic transformation of prostate epithelium. Proc Natl Acad Sci U S A. 2008; 105(6):2105-10. PMC: 2538886. DOI: 10.1073/pnas.0711711105. View

Carter J, Cherry J, Williams K, Turner S, Bates D, Churchill A . Splicing factor polymorphisms, the control of VEGF isoforms and association with angiogenic eye disease. Curr Eye Res. 2011; 36(4):328-35. DOI: 10.3109/02713683.2010.548892. View

Melegh Z, Oltean S . Targeting Angiogenesis in Prostate Cancer. Int J Mol Sci. 2019; 20(11). PMC: 6600172. DOI: 10.3390/ijms20112676. View

Tomlins S, Laxman B, Varambally S, Cao X, Yu J, Helgeson B . Role of the TMPRSS2-ERG gene fusion in prostate cancer. Neoplasia. 2008; 10(2):177-88. PMC: 2244693. DOI: 10.1593/neo.07822. View

Tischer E, Mitchell R, Hartman T, Silva M, GOSPODAROWICZ D, Fiddes J . The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem. 1991; 266(18):11947-54. View

Lin C, Yang L, Tanasa B, Hutt K, Ju B, Ohgi K . Nuclear receptor-induced chromosomal proximity and DNA breaks underlie specific translocations in cancer. Cell. 2009; 139(6):1069-83. PMC: 2812435. DOI: 10.1016/j.cell.2009.11.030. View

Stevens M, Star E, Lee M, Innes E, Li L, Bowler E . The VEGF-A exon 8 splicing-sensitive fluorescent reporter mouse is a novel tool to assess the effects of splicing regulatory compounds . RNA Biol. 2019; 16(12):1672-1681. PMC: 6844573. DOI: 10.1080/15476286.2019.1652522. View

10.

Brenner J, Ateeq B, Li Y, Yocum A, Cao Q, Asangani I . Mechanistic rationale for inhibition of poly(ADP-ribose) polymerase in ETS gene fusion-positive prostate cancer. Cancer Cell. 2011; 19(5):664-78. PMC: 3113473. DOI: 10.1016/j.ccr.2011.04.010. View

11.

Comperat E, Wasinger G, Oszwald A, Kain R, Cancel-Tassin G, Cussenot O . The Genetic Complexity of Prostate Cancer. Genes (Basel). 2020; 11(12). PMC: 7760266. DOI: 10.3390/genes11121396. View

12.

Pernar C, Ebot E, Pettersson A, Graff R, Giunchi F, Ahearn T . A Prospective Study of the Association between Physical Activity and Risk of Prostate Cancer Defined by Clinical Features and TMPRSS2:ERG. Eur Urol. 2018; 76(1):33-40. PMC: 6451672. DOI: 10.1016/j.eururo.2018.09.041. View

13.

Lorenzin F, Demichelis F . Past, Current, and Future Strategies to Target ERG Fusion-Positive Prostate Cancer. Cancers (Basel). 2022; 14(5). PMC: 8909394. DOI: 10.3390/cancers14051118. View

14.

Demichelis F, Fall K, Perner S, Andren O, Schmidt F, Setlur S . TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort. Oncogene. 2007; 26(31):4596-9. DOI: 10.1038/sj.onc.1210237. View

15.

James N, de Bono J, Spears M, Clarke N, Mason M, Dearnaley D . Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med. 2017; 377(4):338-351. PMC: 5533216. DOI: 10.1056/NEJMoa1702900. View

16.

Tombal B, Saad F, Penson D, Hussain M, Sternberg C, Morlock R . Patient-reported outcomes following enzalutamide or placebo in men with non-metastatic, castration-resistant prostate cancer (PROSPER): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2019; 20(4):556-569. DOI: 10.1016/S1470-2045(18)30898-2. View

17.

Ferrara N, Gerber H, LeCouter J . The biology of VEGF and its receptors. Nat Med. 2003; 9(6):669-76. DOI: 10.1038/nm0603-669. View

18.

Filson C, Marks L, Litwin M . Expectant management for men with early stage prostate cancer. CA Cancer J Clin. 2015; 65(4):265-82. DOI: 10.3322/caac.21278. View

19.

Tomlins S, Rhodes D, Perner S, Dhanasekaran S, Mehra R, Sun X . Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005; 310(5748):644-8. DOI: 10.1126/science.1117679. View

20.

Liu Q, Wang S, Wang Z, Tang P, Zhang D, Lan W . Identification of novel somatic fusions of , and in prostate cancer treated with anlotinib and androgen deprivation therapy: A case report. Cancer Innov. 2023; 1(1):114-118. PMC: 10686182. DOI: 10.1002/cai2.11. View